Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach

Abstract:

Studies using high dose testosterone (T) administration in normal men as a
male contraceptive have resulted in azoospermia rates of only 50-70%.
Previous studies of T and progestogen combinations have shown comparable
rates of azoospermia, but have been uncontrolled or used T in doses less
than that associated with maximal suppression of sperm production. We
conducted a randomized, placebo-controlled, single blind trial comparing 6
months of T enanthate administration (100 mg, im, weekly) with the same
dose of T enanthate in conjunction with the progestogen levonorgestrel
(LNG; 500 micrograms, orally, daily) in 36 normal men, aged 20-42 yr (n =
18 in each group). The primary end points were induction of azoospermia or
severe oligospermia (< 3 million sperm/mL). The combination of T plus LNG
was much more effective in suppressing sperm production than T alone.
Sixty-seven percent of the T plus LNG group (12 of 18) and 33% of the T
alone group (6 of 18) achieved azoospermia by 6 months (P = 0.06). Severe
oligospermia or azoospermia developed in 94% of the T plus LNG (17 of 18)
group compared to 61% of the T alone group (11 of 18; P < 0.05). T plus
LNG also suppressed sperm production more rapidly than T alone. Time to
azoospermia was 9.9 +/- 1.0 vs. 15.3 +/- 1.9 weeks in the T plus LNG and T
alone groups, respectively (mean +/- SEM; P < 0.05). Serum high density
lipoprotein cholesterol decreased 21.7 +/- 3.6% in men given T plus LNG (P
< 0.05), compared to only a 1.8 +/- 3.8% decrease in men in the T alone
group. Average weight gain was 5.3 +/- 0.8 kg in the T plus LNG group and
2.3 +/- 0.9 kg in the T alone group (P < 0.05). Acne and increase in
hemoglobin were similar in the two groups. We conclude that combination
hormonal therapy with T plus a progestogen might offer a reversible male
contraceptive approach with a more rapid onset of action and more reliable
induction of both azoospermia and severe oligospermia than T alone.